Expression of genes encoding neuropeptides and enzymes in the brain, with emphasis on the hypothalamus, are being studied. We successfully created a knock-out of the oxytocin (OT) gene in mice through homologous recombination. These mice demonstrate that OT is absolutely required for milk ejection, but not mammary gland development, fertility or parturition. We have determined that OT participates in the regulation of mammary gland cellular development and apoptosis. We are currently developing a conditional OT receptor knock-out mouse to look at the role of OT from another vantage point. We have determined how to use the OT gene to express in a cell-specific way foreign genes in the mouse brain. We have looked at content release from pituitary neurosecretosomes in real time using green fluorescent protein as a reporter. Other genes are being targeted to the OT neurons in an attempt to perturb their functioning and gain understanding of the OT neuronal physiology. We have also knocked out the vasopressin 1b receptor in mice. They are growing normally and we are studying them using a variety of different physiological and behavioral challenges.